Ion mobility spectrometry (IMS) is a gas-phase ion separation technique in which ions become separated in time and space as they travel through a drift cell of known length containing a buffer gas of known composition, pressure and temperature. An IMS system in general includes an ion source, the drift cell, and an ion detector. The ion source ionizes molecules of a sample of interest and transmits the resulting ions into the drift cell. After traveling through the drift cell, the ions arrive at the ion detector. In low-field drift-time IMS techniques, ions travel through the drift cell under the influence of a uniform DC voltage gradient established by electrodes of the drift cell. While the electric field moves the ions through the drift cell, the ions experience a drag force due to collisions with the stationary buffer gas molecules in the drift cell. The drag force acts against the electrical force that moves the ions. The drag force experienced by an ion depends on its collision cross section (CCS or Ω), which is a function of the ion's size and shape (conformation), and on its electrical charge and (to a lesser extent) mass. Ions with larger CCSs are retarded more easily by collisions with the buffer gas. On the other hand, multiply charged ions move through the buffer gas more effectively than singly charged ions because multiply charged ions experience a greater force due to the electrical field. The different CCSs of the separated ions can be correlated to their differing gas-phase mobilities through the buffer gas by the well-known Mason-Schamp equation.
Moreover, the different drift times of the separated ions through the length of the drift cell can be correlated to their differing mobilities. As the separated ions arrive at the ion detector, the ion detector counts the ions and measures their arrival times. The ion detector outputs measurement signals to electronics configured for processing the output signals as needed to produce a user-interpretable drift spectrum. The drift spectrum is typically presented as a plot containing a series of peaks indicative of the relative abundances of detected ions as a function of their drift time through the drift cell. The drift spectrum may be utilized to identify and distinguish different analyte species of the sample.
IMS may be coupled with one or more other types of separation techniques to increase compound identification power, such as gas chromatography (GC), liquid chromatography (LC), or mass spectrometry (MS). For example, an IMS drift cell may be coupled in-line with an MS system to form a combined IM-MS system. An MS system in general includes a mass analyzer for separating ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), followed by an ion detector. An MS analysis produces a mass spectrum, which is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. The mass spectrum may be utilized to determine the molecular structures of components of the sample. An IM drift cell is often coupled to a time-of-flight mass spectrometer (TOFMS), which utilizes a high-resolution mass analyzer (TOF analyzer) in the form of an electric field-free flight tube. An ion extractor (or pulser) injects ions in pulses (or packets) into the flight tube. Ions of differing masses travel at different velocities through the flight tube and thus separate (spread out) according to their differing masses, enabling mass resolution based on time-of-flight.
In a combined IM-MS system, the ion source is followed by the IM drift cell, which in turn is followed by the mass analyzer and then the ion detector. Thus, ions are separated by mobility prior to being transmitted into the MS where they are then mass-resolved. Performing the two separation techniques in tandem is particularly useful in the analysis of complex chemical mixtures, including biopolymers such as polynucleotides, proteins, carbohydrates and the like. For example, the added dimension provided by the IM separation may help to separate ions that are different from each other but present overlapping mass peaks. The data acquired from processing a sample through an IM-MS system may be multi-dimensional, typically including ion abundance, acquisition time (or retention time), ion drift time through the IM drift cell, and m/z ratio as resolved by the MS. This hybrid separation technique may be further enhanced by coupling it with LC, thus providing an LC-IM-MS system.
Overlapping (or intermingling) between sequentially adjacent ion packets in the IM drift cell or TOF flight tube occurs when the slower ions of one ion packet are overtaken by faster ions of a subsequently injected ion packet. Consequently, ions from different ion packets arrive at the ion detector at the same instant of time, even though such ions have different mobilities and/or m/z ratios. The resulting measurement data acquired by the ion detector are convoluted, making the drift spectra and/or mass spectra difficult to interpret. Conventionally, this problem is avoided by operating IMS and TOFMS systems according to a “pulse and wait” approach, in which the injection rate of ion packets into the IM drift cell or the TOF flight tube is kept low enough to avoid overlapping. For example, after injecting an ion packet, the next ion packet may not be injected until the first ion packet has reached the ion detector. The pulse and wait approach thus suffers from a low duty cycle, as well as excessive ion losses between injections (at the ion gate preceding the IM drift tube or the ion pulser preceding the TOF flight tube) and thus low instrument sensitivity, particularly when a continuous-beam ion source is utilized.
Multiplexing (multiplexed injection) techniques are being developed as an improvement over the pulse and wait approach. With multiplexing, also known as multi-pulsing or over-pulsing, the injection of ion packets into the IM drift cell or the TOF flight tube is done at a high enough rate that multiple ion packets are present in the IM drift cell or TOF flight tube at the same time. Multiplexing causes overlapping between ion packets. However, multiplexing techniques address the problem of convoluted measurement data by applying some form of a deconvolution (or demultiplexing) process to the measurement data, thereby enabling a single drift time spectrum or TOF spectrum to be recovered from the measurement data. Of particular interest are deconvolution techniques based on the Hadamard transform (HT), although other types of transforms may alternatively be utilized. As an example of a HT technique, the ion packets are injected according to a pseudo-random sequence (PRS) of binary 1 ‘s and 0's, where the 1’ s correspond to “gate-open” (injection) events and the 0's correspond to “gate-closed” periods of time. The PRS is then used to generate an N×N Hadamard matrix, where N is the number of binary elements of the PRS. The Hadamard matrix in turn is used to generate an inverse Hadamard matrix. The inverse Hadamard matrix is then applied to the convoluted measurement data to extract a single array (or vector) of data from which a single, deconvoluted (or demultiplexed) spectrum may be generated.
One problem observed in the application of transform-based deconvolution techniques is the presence of noise in the raw measurement data to be deconvoluted. These noise components can cause inaccuracies in the deconvoluted data and subsequently generated spectra. Therefore, there is a need for IMS, MS, and IM-MS systems, and data acquisition methods for IMS, MS, and IM-MS, capable of performing deconvolution with less sensitivity to noise.